The prognosis of pancreatobiliary malignancies with biliary obstructions is generally dismal because of unresectability at the time of presentation and poor response to chemotherapy and radiotherapy. Intrabiliary stenting is currently the best option for the treatment of most malignant biliary obstructions. However, the short term durability of biliary stents necessitates repeated interventions and longer hospital stays with associated high economic burden. In addition, current techniques for systemic chemotherapy do not permit delivery of doses sufficient for effective response at the target sites without substantial undesired toxicities to other organ systems. In the present project, we aim to overcome these problems with currently available medical and surgical treatments of malignant common bile duct (CBD) obstructions. Based on our previous extensive experience with a novel intraluminal MR imaging (MRI)/radiofrequency heating (RFH) prototype system, we are going to establish a new interventional technique. This innovative approach involves (a) intrabiliary MRI-guided local delivery of high-dose chemotherapeutic agents into the CBD wall and adjacent tissues; and (b) intrabiliary MRI-guided, RFH-enhanced local chemotherapy of malignant CBD obstructions. To achieve this goal, we propose three milestones: (i) optimization of the new intrabiliary MRI/RFH prototype system; (ii) preclinical validation of the feasibility of using the new technology to guide and enhance chemotherapeutic drug delivery into the CBD wall and adjacent tissues; and (iii) translation of this novel technology to clinical practice to treat the patients with malignant biliary obstructions. We are convinced that the success of this project could lead to significant breakthroughs in the management of malignant biliary diseases using MRI/RFH-interactive interventional oncologic techniques. Further expansion of this new technology should pave the road to advances in other areas of clinical translational research, including heat-enhanced gene therapy, temperature-sensitive therapies using targeted nanoparticles and peptides, photodynamic therapy, and radiation therapy. Finally, the success of this project should lay the groundwork for development of new technologies to treat obstructive diseases in other luminal systems such as the urinary tract and gastrointestinal tract.